The mixing of components, such as different types of solids, liquids and/or gases, has a number of applications in different industries. For example, in the pharmaceutical industry, different types of drugs are mixed together. In the medical field, body fluids (such as blood) and/or drugs are typical components that are mixed. In the semiconductor field, wet solutions are combined with abrasives to make slurries. The food industry also incorporates mixing operations into a number of applications. For example, water is mixed with dehydrated food for the rehydration of such food.
However, in these and other industries, the components that are mixed may be hazardous, dangerous, infectious and/or require high levels of purity. For example, in the pharmaceutical and/or medical industries, the components that are to be mixed may be toxic. Additionally, in a number of situations, the handling of powders may be dangerous because of the possibilities of inhalation of such powders. In the medical field, individuals that handle body fluids, such as fluids that are HIV-infected, do so while attempting to avoid direct contact with these fluids. Furthermore, in the semiconductor industry, handling of chemicals is avoided to reduce the potential for forming particulate and introducing impurities.
Conventional mixing devices generally involve a glass tank for components that are of small volumes and a stainless steel tank for components of larger volumes. These tanks often include a screw to agitate and maintain powders within suspension. Such screws are also used to homogenize multiphase solutions. Prior to use, these mixing tanks must be washed and sterilized. Typically, an autoclave is used for washing and sterilizing small volume tanks, while a water steam-based operation is employed for washing and sterilizing larger volume tanks. When preparing batches of post-etch residue removers for semiconductor applications, introduction of contaminants must be excluded at all levels of processing to decrease particulate formation, which leads to device failure. These wash, sterilize, and process operations, which are essential to the specified technologies, are typically time-consuming and expensive, and require highly qualified individuals for their performance. Further, periodic maintenance of mixing devices associated with the various technologies must be performed to ensure proper operation. In certain cases, washing/sterilizing operations as well as the maintenance of these mixing devices may represent more than a third of the total cost of operating and maintaining such mixing devices, which may be prohibitively expensive for given applications. Additionally, mixing of components may cause the pressure to increase within these conventional mixing devices. If this increased pressure is not accounted for, then the mixing of such components may become dangerous, such as the possibility that the tanks could break apart/explode due to this internal pressure. Moreover, with the use of many mixing devices currently employed to mix pharmaceuticals, the displacement of some pharmaceutical outside the mixing device cannot be eliminated, and therefore the amount of pharmaceutical remaining inside the mixing device, after mixing, may not be sufficiently accurate or precisely known. This is problematic when the FDA requires the administration of such a pharmaceutical in precise, accurate and known quantities.
Due to their multiple advantages, disposable containers are becoming increasingly useful in many industrial applications, particularly as storage containers.
In biological processing, there is an ever-increasing need for disposable products, such as storage bags, which can range in size from 10 to more than 3,000 liters. Current uses include, among others, storage of products or components awaiting disposition to further processing steps such as, for example, purification. Often, however, the stored products or components are mixtures, which, over time, may separate out into phases or components. Emulsions and suspensions, for example, are particularly predisposed to such phase separations.
Current industry standards require remixing, regeneration and/or revalidation of a suspension or emulsion before further processing can resume. In order for remixing to occur without removing the contents from a storage bag, a magnetic stir bar is used. Often, the duration of the regeneration/revalidation step is up to several hours, and the quality of mixing is not uniformly high. Additionally, such a process is prone to particle generation inside the bag that contaminates the formulation therein.
Alternatively, a recirculation loop may be employed to regenerate mixtures, such as emulsions or suspensions, whereby liquid separated from the bulk mixture is repeatedly drained from the foot or base of the storage bag and refilled through the top of the bag. In addition to being time-consuming, such an alternative process requires the container to be opened and resealed.
As noted above, mixing of materials continues to face challenges in many industrial applications. Therefore, systems utilizing disposable elements and providing storage and mixing capabilities are needed. Desirable systems should provide benefits including any of the following: reduced labor requirements, lower production costs, and improved product quality in mixing applications.
Certain solid-liquid and liquid-liquid mixing applications are conventionally performed in open vessels lined with disposable liner materials, with the mixing energy provided by a motor driven (shear) impeller that is reused and typically cleaned between uses. To provide adequate mixing performance, high rotational velocities (e.g., high RPMs) are often used. The utility of such systems is limited because some products cannot handle high shear forces, yet still require high levels of induced turbulence for full dissolution. Additionally, high shear mixing may also cause foaming, which is undesirable in certain applications. There exists a need for improved mixing systems adapted to avoid these shortcomings.
In systems requiring sterile mixing, it may be desirable to provide a closed mixing vessel. As various contents are supplied to and extracted from the mixing vessel, or as various reactions occur within the vessel, the pressure within the vessel may change substantially. Particularly if flexible or collapsible materials are used for the vessel walls, the vessel may expand or contract with these changes in pressure. Taken to an extreme, such volumetric changes may impede movement of the mixing element and thus hinder mixing, or may cause the vessel to rupture. While venting the vessel to atmosphere would eliminate such problems, such ventilation would contaminate the previously sterile environment of the closed container. Alternatively, conventional pressure control systems might appear to present a satisfactory solution, but their implementation may be hindered with disposable mixing vessels such as those constructed with film-based liner materials due to the impracticability of interfacing pressure sensors with such materials.